Increased intraocular and systemic levels of the angiogenic factor vascular endothelial growth factor (VEGF) is associated with new vessel growth in the eye, such as diabetic retinopathy. Recent work using immunopathologic techniques have shown that VEGF is upregulated in both experimentally induced uveitis and in uveitis eyes as well, with no evidence of neovascularization. This pilot study evaluated the level of VEGF in the blood of uveitic patients with and without cystoid macular edema. This level was determined also in the ocular fluid of those patietns undergoing ocular surgery. We measured the VEGF concentration in the aqueous humor of 20 uveitis patients (9 with and 11 without CME), and in the plasma of 40 uveitis patients (20 with and 20 without CME) and 20 healthy volunteers. Results: Mean aqueous humor VEGF concentrations for uveitis patients with and without CME were 152.3 and 109.5 pg/mL, p=0.048. Mean plasma VEGF concentrations in uveitis patients with and without CME and in healthy volunteers were 32.2, 29.6, and 55.0 pg/mL. Uveitis patients had lower plasma VEGF levels than healthy volunteers, p=0.002. Conclusions: VEGF concentration is elevated in the aqueous humor of uveitis patients with CME. Plasma VEGF concentration is reduced in uveitis patients on systemic immunosuppression. Because of these observations, we have begun testing the efficacy of ???-tocopherol (vitamin E), a potent inhibitor of the protein kinase C pathway in vascular endothelial growth factor (VEGF) induced vascular permeability, for the treatment of uveitis-associated macular edema. This is performed using a double-masked, randomized study in which uveitis patients with macular edema will receive either ???-tocopherol or placebo. Patients will receive 1600IU/day of Vitamin E or placebo for 4 months. The primary outcome will be a visual acuity increase of 10 letters or more from baseline to month 4. Secondary outcomes are total area of leakage and macular height as determined by fluorescein angiography, changes in CME as measured by stereoscopic color photographs, optical coherence tomography (OCT), the need for periocular injections or additional systemic immunomodulatory medications, and the NEI VFQ summary score. Patients have been actively recruited and the number of patients required for an initial evaluation by the Data and Safety Committee will be reached shortly. Because it remains a masked study no information is yet available.